towards personalized medicine in estonia
DESCRIPTION
Overview of Estonian opportunities to move towards more personalized medicine with help of Estonian Biobank, national E-Health solutions and state-wide information exchange framework. Presented at international conference "E-health - integration of IT and medicine" in Tartu 15.09.2013. http://mug.ee/ehealth/TRANSCRIPT
Towards personalized
medicine in Estonia
Erkki Leego
IT adviser
Estonian Genome Center,
University of Tartu
Biobanks
• Biobank – An organized collection of human biological
material and associated information stored for one or more research purposes
• Population biobank – The collection has a population basis
– To supply biological materials or data derived therefrom for multiple future research projects
– It contains biological materials and associated personal data
Genetic research
• Most complex diseases are caused by a large
number of combined effects from genes,
lifestyle, and the environment
• New discoveries and development of tools
depend on studies of large collections of well-
documented, up-to-date epidemiological and
clinical data accompanied by biological
material from individuals
Estonian Biobank
• Estonian Genome Center, University of Tartu
• A prospective, longitudinal, population biobank with health record and biological materials
• Established in 2000
• 52,000 gene donors recruited -5% of the adult population
• Supported directly by the government
• Estonian Human Genes Research Act
Population pyramid (50155 participants)
02680536080401072013400
0100200300400500600700
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
52
54
56
58
60
62
64
66
68
70
72
74
76
78
80
82
84
Count EGCUT
Ag
e
Female
EGCUT
Estonia 2007
0 2680 5360 8040 10720 13400
0 100 200 300 400 500 600 700
18
20
22
24
26
28
30
32
34
36
38
40
42
44
46
48
50
52
54
56
58
60
62
64
66
68
70
72
74
76
78
80
82
84
Count EGCUT
Male
EGCUT
Estonia 2007
Count Estonia Count Estonia
Data “infrastructure” for
research
• Good quality data collection – Biomedical data (DNA, plasma, WBC)
– Phenotype
– Genealogy
– Epidemiology data
– Genotypes
• Open to various research projects
• Well defined procedures for data release
• Usable next 30 years
Questionnaire of EGCUT
Personal data
Place of birth
Place of residence
Nationality
Education
Occupation
Genealogy
Parents
Children
Siblings
Grandparents
Health behavior
Smoking and alcohol
Personality inventory NEO-
PI-3
Physical activity
EQ-5D
Nutrition
Health self-assessment
Chronotype questionnaire
MCTQ
Diseases
Diagnosis
ICD – 10
Treatment
ATC
Psychiatry module
M.I.N.I. and SSP
Questions about diabetes
Questions
about c/v diseases
Objective data
Height & weight
Blood pressure
Pulse
Handedness
Waist
Hip
Diagnoses in the database (50155 participants)
64245
8928
3106
12677
10766
11833
19918
13833
40209
60778
39490
12585
37322
21170
3352
134
1405
3202
5710
1610
619
0 10000 20000 30000 40000 50000 60000 70000
Certain Infectious And Parasitic Diseases A00-B99
Neoplasms C00-D48
Diseases Of Blood And Blood-Forming Organs And Certain…
Endocrine, Nutritional And Metabolic Diseases E00-E90
Mental, Behavioural Disorders F00-F99
Diseases Of The Nervous System G00-G99
Diseases Of The Eye And Adnexa H00-H59
Diseases Of The Ear And Mastoid Process H60-H95
Diseases Of The Circulatory System I00-I99
Diseases Of The Respiratory System J00-J99
Diseases Of The Digestive System K00-K93
Diseases Of The Skin And Subcutaneous Tissue L00-L99
Diseases Of The Musculoskeletal System And Connective Tissue…
Diseases Of The Genitourinary System N00-N99
Pregnancy, Childbirth And The Puerperium O00-O99
Certain Conditions Originating In The Perinatal Period P00-P96
Congenital Malformations, Deformations, And Chromosomal…
Symptoms, Signs And Abnormal Clinical And Laboratory Findings,…
Injury, Poisoning And Certain Other Consequences Of External…
Factors Influencing Health Status And Contact With Health Services…
External Causes Of Morbidity And Mortality V01-Y98
•In average a participant has
reported 7.8 different diagnoses
•98.3% of participants have
reported at least one disease
Education: the Estonian population vs. EGCUT (50155 participants)
0 10 20 30
Education unknown
No elementary education
Elementary education
Basic education
Secondary education
Professional secondaryeducation
Higher education
Scientific degree
%
Estonian population EGCUT
Using data
• Today’s focus is on Genome Wide Association Studies (GWAS) – "Genetic variants in novel
pathways influence blood pressure and cardiovascular disease risk„
– "Complement Factor H Polymorphism in Age-Related Macular Degeneration"
– …
• Next focus on rich phenotype, including health behavior and sensor data
• Then personalized medicine solutions
Example. Coffee drinking habits
1: 2002-2005; 2: 2007-2008; 3: 2009-2010
Genetic „map“ of Estonia
-0,03
-0,02
-0,01
0
0,01
0,02
0,03
0,04
-0,02 -0,01 0 0,01 0,02 0,03
PC
2
PC1
Põhja-Eesti
Lõuna-Eesti
Põhja
Lõuna
Secure data handling
Courier
Filled questionnairesPersonal data, health data, genealogy data.
Consent. Transportation code. Information encrypted.
Consent (p
aper fo
rm).
Bio
logic
al s
am
ple
s.
Coding center
Memory stick
Consent forms. Questionnaires.
Receptionist
New barcode
High security area Access to database
Scientists
Health data. No identification
data.
Health data and identification
data
National Digital Health Record DB & registries
Operative database
Phenotype database
Data collector ISCommunication server
Laboratory ISCryo Preservation – MAPI
Coding center IS
Coding challenges
EXTERNAL DATABASESdata collecting
BIOSAMPLES DATAmanagement
PERSONAL-, GENEALOGY-, HEALTH DATA
Formatting for integration, deindentification
DKOOD
I U T L
I
HEALTH DATAdata collecting
I T
PHENOTYPESintegration, quality control,
analysis
U L
CODING CENTRE
H
GENOTYPESraw data, , quality control,
analysis
U L
PROJECT-BASED RESEARCH
L
CODE RELATIONS
U D L V
genotypes, fenotypes, biosamples, analysis
D V
BIOSAMPLES DATAanalysis
L
IKOOD UKOOD TKOOD LKOOD VKOOD
FOLLOW UPcoordination
D
FEEDBACKPERSONALIZED MEDICINE
genotypes, fenotypes, biosamples, analysis
DATA REALEASE
BIOSAMPLES DATAlogistics
LT
H
HKOOD
D V
D V
National Digital Health Record DB
Online access to database
Scientists
Health data. No identification
data
Phenotype database
Patient Portal National DHR
Cancer Registry
Citizen RegistryCauses of Death Registry
Participant
Participant
Participant
Participant
Participant
Participant
Participant
EGCUT databasePersonal health
information
Additional questions.
Timeline data
Updated phenotype
data
Participant
Data release
EGCUT IS 2011-2015
Primary care physician
...
Ver. 5.0
Public opinion and awareness of the EGCUT 2001-
2013
Illumina Genome Analyser
10 Gbit Network10 Gbit Network
EGCUT Network High Perfomance Computing Centre
10Gbit
Coding Centre
InfrastructureServers
DATABASESData Colletor
Phenotype DatabaseLaboratory IS
InfrastructureServers24 Core,
192GB RAM, 1,76TB HDD
System Storage
System Storage Tape Library 1,2PB storage
Coding
Centre IS
Analyser servers184 Core, 2048GB RAM
Backup Server
16 Core1,2TB HDD24GB RAM
EGCUT servers and storageApril 2013
· 15 servers
· Datastorage 1,1 PB harddrives
· 1,2 PB system storage tape library
MAPI
Hamilton ASMASM Store
ASM Server
Datastoragewith servers
1,1 PB HDD
19 2318 2217 2116 2011 159 13 10 148 123 71 5 2 6402498-B24
System x3650 M3
1 2
3 4
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
System x3650 M3
1 2
3 4
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
19 2318 2217 2116 2011 159 13 10 148 123 71 5 2 6402498-B24
Computing power
· 3260 processor core
· 8,2 TB RAM
OperativeDatabase
HPC Cluster „Aurumasin“
52 node,512 Core,
2,3TB RAM,
50TB HDD
HPC Cluster „Vedur“80 node,
2560 Core, 3,75TB RAM,
110TB HDD
Example of
personal genetic
information
Ref: https://www.23andme.com/you/
Risk dependence on age
• Men ages 0-79 • Men ages 40-49
What can I do?
Ancestery and relatives
• Ancestery
• DNA relatives
Towards more
personalized
medicine
Calculating personal genetic
risks
Person
DNA
Personal disease risks
Personal variants
Database of known risk markers
Conditions for feedback
• Treatable health conditions with genetic
factors
– Melanoma
– Prostate cancer
– Type I and II Diabetes
– Lupus
– Age-Related Macular Degeneration
– Iron Overload/Hemochromatosis
Pharmacogenomics
• How genetic makeup affects an individual’s
response to drugs
• Aim is to ensure maximum efficacy with
minimal adverse effects
• Drugs and drug combinations can be
optimized for each individual's unique genetic
makeup
• Reduces cost of healthcare
New devices for self monitoring
• ECG adaptor for
smartphone
• Blood clucose sensors
• Sleep monitoring
• Ultrasound device Vscan
Ref: E. Topol. http://www.ted.com/talks/eric_topol_the_wireless_future_of_medicine.html
Challenges and issues
• Awareness doctors and patients
• New technologies and data empower patient with more possibilities to manage own health
• Ethical issues – Right to know and right not to know
– Treatable and non-treatable conditions
• Not enough knowledge about associations between DNA variants and diseases
• Large work-load to keep database of known risk markers updated
Estonia’s unique
starting point
Estonian E-services
• 99% of bank transfers are performed electronically
• 94% of income tax declarations made via the e-Tax Board
• 24% of votes were cast over the internet on 2011
• 62% persons have completed the e-census 2012
• 2000: Launch of e-Tax Board
• 2000: Launch of m-Parking
• 2002 : Introduction of national electronic ID-Card
• 2005: i-Voting was introduced
• 2007: Introduction of m-ID
• 2007: Launch of e-Police system
• 2008: Launch of e-Health system
• 2010: Launch of e-Prescription
• 2012: e-census
Tools and enablers of
information exchange
• One universal national identification code – Registries and databases use same code to uniquely
identify persons
• National PKI infrastructure
• The Estonian ID card – Smartcard with two digital certificates
• National Data Exchange Layer X-Road
• Obligatory national data security framework
• High public acceptance and trust – No public incidents or misuses (10 years)
Estonian information system
PHARMACIES AND
FAMILY DOCTORS
2009
X-Road, ID-card, State IS Service Register
HE
AL
TH
CA
RE
BO
AR
D
- H
ealth c
are
pro
vid
ers
- H
ealth p
rofe
ssio
nals
- D
ispensin
g c
hem
ists
ST
AT
E A
GE
NC
Y O
F M
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ICIN
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Codin
g C
entr
e
- H
andle
rs o
f m
edic
ines
PO
PU
LA
TIO
N R
EG
IST
ER
PH
AR
MA
CIS
2010 january
BU
SIN
ES
S R
EG
IST
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HO
SP
ITA
LS
2
00
9
FA
MIL
Y D
OC
TO
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2
00
9
SC
HO
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NU
RS
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2010 s
epte
mber
EM
ER
GE
NC
Y M
ED
ICA
L S
ER
VIC
E
20
11
NATION- WIDE
HEALTH
INFORMATION
EXCHANGE PLATFORM
2008 december
PRESCRIPTION
CENTRE
2010 january
PATIENT PORTAL
2009
X-ROAD
GATEWAY
SERVICE
2009
The Estonian ID card
• The ID card is a mandatory ID document for all Estonian residents from the age of 15
• Enables secure digital authentication and signing
• A digital signature has the same legal consequences as a hand-written signature
• Does not have any additional information – No bank account, no health information etc.
• Active cards: 1 209 594 (13.09.2013) – Estonian Population 1 286 540 (01.01.2013)
– Estonia has been issuing electronic ID cards from January 1st 2002
Public Key Infrastructure PKI
• PKI or the public key infrastructure enables secure digital authentication and signing
• The infrastructure also allows forwarding data by using an encrypting key pair: a public encryption key and a private decryption key
• In Estonia, this technology is used in relation with electronic identity (ID card, mobile ID, digital ID)
• Certification Service and Time-stamping Service provider is non-governmetal
Data Exchange Layer X-Road
• Technical and organizational environment, which enables secure Internet-based data exchange between the state’s information systems
Conclusions
• Estonia has great potential to implement state
level personalized medicine solutions
– Genetic research with 5% of population genetic
and continuously updated phenotype information
– Nation wide Health Information Exchange platform
– 10 years of experience of national level e-services
(PKI, X-Road, ID-card, security framework)
– High level public trust and acceptance